PTP1B Inhibition Improves Mitochondrial Dynamics to Alleviate Calcific Aortic Valve Disease Via Regulating OPA1 Homeostasis

Feng Liu; Jinyong Chen; Wangxing Hu; Chenyang Gao; Zhiru Zeng; Si Cheng; Kaixiang Yu; Yi Qian; Dilin Xu; Gangjie Zhu; Jing Zhao; Xianbao Liu; Jian'an Wang

doi:10.1016/j.jacbts.2022.03.002

PTP1B Inhibition Improves Mitochondrial Dynamics to Alleviate Calcific Aortic Valve Disease Via Regulating OPA1 Homeostasis

JACC Basic Transl Sci. 2022 Jul 25;7(7):697-712. doi: 10.1016/j.jacbts.2022.03.002. eCollection 2022 Jul.

Authors

Feng Liu^{1

2}, Jinyong Chen^{1

2}, Wangxing Hu^{1

2}, Chenyang Gao^{1

2}, Zhiru Zeng^{1

2}, Si Cheng^{1

2}, Kaixiang Yu^{1

2}, Yi Qian^{1

2}, Dilin Xu^{1

2}, Gangjie Zhu^{1

2}, Jing Zhao^{1

2}, Xianbao Liu^{1

2}, Jian'an Wang^{1

2}

Affiliations

¹ Department of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Key Laboratory of Cardiovascular Disease of Zhejiang Province, Hangzhou, China.

Abstract

There are currently no pharmacological therapies for calcific aortic valve disease (CAVD). Here, we evaluated the role of protein tyrosine phosphatase 1B (PTP1B) inhibition in CAVD. Up-regulation of PTP1B was critically involved in calcified human aortic valve, and PTP1B inhibition had beneficial effects in preventing fibrocalcific response in valvular interstitial cells and LDLR^-/- mice. In addition, we reported a novel function of PTP1B in regulating mitochondrial homeostasis by interacting with the OPA1 isoform transition in valvular interstitial cell osteogenesis. Thus, these findings have identified PTP1B as a potential target for preventing aortic valve calcification in patients with CAVD.

Keywords: CAVD, calcific aortic valve disease; HFD, high-fat diet; L-OPA1, long form of OPA1; OPA1, optic atrophy 1; PTP1B, protein tyrosine phosphatase 1B; S-OPA1, short form of OPA1; TGFβ, transforming growth factor β; VIC, valvular interstitial cell; calcific aortic valve disease; mitochondrial biogenesis; optic atrophy 1; protein tyrosine phosphatase 1B; valvular interstitial cells; β-GA, β-glycerophosphate acid.